Abstract Title:

Activation of the Nrf2 Signaling Pathway Involving KLF9 Plays a Critical Role in Allicin Resisting Against Arsenic Trioxide-Induced Hepatotoxicity in Rats.

Abstract Source:

Biol Trace Elem Res. 2017 Mar ;176(1):192-200. Epub 2016 Aug 25. PMID: 27561292

Abstract Author(s):

Daqian Yang, Zhanjun Lv, Haili Zhang, Biying Liu, Huijie Jiang, Xiao Tan, Jingjing Lu, Ruiqi Baiyun, Zhigang Zhang

Article Affiliation:

Daqian Yang


Arsenic trioxide (As2O3) is both the most prevalent, naturally occurring inorganic arsenical threatening human health and an efficient therapeutic for acute promyelocytic leukemia. Regretfully, As2O3-treated cancer patients often suffer from hepatotoxicity. While effective antioxidant and anticarcinogenic actions of allicin have previously been demonstrated, studies indicating how allicin affects As2O3-induced hepatotoxicity and arsenic accumulation are lacking. Our study, for the first time, elaborates potential details of the hepatoprotective mechanisms of allicin against As2O3-induced liver injury. Wistar rats were administrated allicin (30 mg/kg) 1 h before As2O3 (3 mg/kg) by daily gavage for 2 weeks. Our results indicate that allicin ameliorated As2O3-induced liver dysfunction, oxidative stress, and arsenic accumulation in the liver. Meanwhile, allicin decreased NF-κB level and upregulated expression of proteins reduced by As2O3 including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1, and Krüppel-like factor 9 (KLF9). In addition, allicin promoted B cell lymphoma-extra large expression and suppressed B cell lymphoma-2-associatedX protein levels regulated by As2O3. However, neither allicin nor As2O3 affected cytochrome P450 2E1 mRNA expression. In conclusion, allicin attenuated As2O3-induced hepatotoxicity by activating the Nrf2 signaling pathway involving KLF9 to inhibit oxidative stress and apoptosis. Our findings elucidate a detailed mechanism by which allicin provides protection against As2O3-induced liver injury and support its potential role as an adjunctive therapy for patients suffering from chronic arsenic exposure.

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Sayer Ji
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